The retina, like many other regions of the nervous system, is subject to a variety of inherited and acquired degenerative conditions. These conditions often result in the degeneration of the photoreceptors, the main light sensing cells in the retina. Despite the loss of photoreceptors, the inner retinal circuitry is intact for many year, and this has led to the possibility of photoreceptor replacement as a potential therapy. Cell replacement strategy is important as the loss of photoreceptors in the mammalian retina is not associated with any effective regeneration from resident cells. A potential source of cellular replacement could be pluripotent stem cells. There are a number of groups looking into the potential of stem cell derived RPE including an approved clinical trial for RPE cell replacement for AMD and Stargardt dystrophy. However, as the disease progresses to vision loss, patients will require replacement of the lost photoreceptor cells as well. Although a number of groups have shown integration of photoreceptors in the mouse retina, the overall efficiency is really low. Additionally, the role of the microglia in this process has largely been unexplored. This proposal aims to look at the role of microglia-derived neurotrophic factors in both retinal repair and regenerative medicine. We will use a cross-species approach to identify and carry out basic studies in flies and apply the result in mammalian retinas.
Retinal degenerations affect millions of people in the US. The disease poses a significant financial burden on the society accounting for over $100 billion in direct costs in the US. The current project aims to look at ways to slow disease progression and enhance stem cell-based cell replacement strategy for these patients.
|Zhu, Jie; Reynolds, Joseph; Garcia, Thelma et al. (2018) Generation of Transplantable Retinal Photoreceptors from a Current Good Manufacturing Practice-Manufactured Human Induced Pluripotent Stem Cell Line. Stem Cells Transl Med 7:210-219|
|Zhu, Jie; Lamba, Deepak A (2018) Small Molecule-Based Retinal Differentiation of Human Embryonic Stem Cells and Induced Pluripotent Stem Cells. Bio Protoc 8:|
|Neves, Joana; Zhu, Jie; Sousa-Victor, Pedro et al. (2016) Immune modulation by MANF promotes tissue repair and regenerative success in the retina. Science 353:aaf3646|